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Biomedical subjects

E Jager

Publications and source records attributed to E Jager.

14 recordsLinked to original sources

The clinical benefit of pegylated liposomal doxorubicin in patients with metastatic breast cancer previously treated with conventional anthracyclines: a multicentre phase II trial.

This study evaluates the clinical benefit of pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC), previously treated with conventional anthracyclines. Seventy-nine women with MBC previously treated with anthracyclines received PLD 50 mg m(-2) every 4 weeks. All patients were previously treated with chemotherapy and 30% of patients had > or =3 prior chemotherapies for metastatic disease. Patients were considered anthracycline resistant when they had disease progression on anthracycline therapy for MBC or within 6 months of adjuvant therapy. The overall clinical benefit rate (objective response+stable disease > or =24 weeks) was 24% (16.1% in patients with documented anthracycline resistance vs 29% in patients classified as having non-anthracycline-resistant disease). There was no difference with respect to the clinical benefit between patients who received PLD >12 months and those who received PLD < or =12 months since last anthracycline treatment for metastatic disease (clinical benefit 25 vs 24.1%, respectively). Median time to progression and overall survival were 3.6 and 12.3 months, respectively. The median duration of response was 12 months, and the median time to progression in patients with stable disease (any) was 9.5 months. Fourteen patients (17.7%) had a prolonged clinical benefit lasting > or =12 months. In conclusion, PLD was associated with an evident clinical benefit in anthracycline-pretreated patients with MBC.

Adult↗

A Systemic Hyperthermia Oncologic Working Group trial. Ifosfamide, carboplatin, and etoposide combined with 41.8 degrees C whole-body hyperthermia for metastatic soft tissue sarcoma.

BACKGROUND: Based on earlier clinical and preclinical studies, we conducted a phase II trial in metastatic sarcoma patients of the combination of 41.8 degrees C (x60 min) radiant heat (Aquatherm) whole-body hyperthermia (WBH) with 'ICE' chemotherapy. The ICE regimen consists of ifosfamide (5 g/m(2)), carboplatin (300 mg/m(2)) and etoposide (100 mg/m(2)), concurrent with WBH, with etoposide also on days 2 and 3 post-WBH. METHODS: Therapy was delivered every 4 weeks for a maximum of 4 cycles. All patients received filgrastim or lenograstim. RESULTS: Of 108 patients enrolled as of September 2001, 95 are evaluable for response. Of the evaluable patients (mean ECOG performance status approximately 1; mean age 42.3; 58% male) 33 had no prior therapy for metastatic disease, and 62 were pretreated (mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For no prior therapy, the response rate was 36%; in pretreated patients it was 24%. The median overall survival by Kaplan-Meier estimates was 393 days (95% CI 327, 496); the median time to treatment failure was 123 days (95% CI 77, 164). The major toxicity (287 cycles) was grade 3 or 4 neutropenia and thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7 episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving disease progression and ureteral obstruction. CONCLUSION: These results are consistent with continued clinical investigation of this combined modality approach.

Adolescent↗

Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele.

NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by strong CD8(+) T cell responses against HLA-A2-restricted epitopes. To broaden the range of cancer patients who can be assessed for immunity to NY-ESO-1, a general method was devised to detect T cell reactivity independent of prior characterization of epitopes. A recombinant adenoviral vector encoding the full cDNA sequence of NY-ESO-1 was used to transduce CD8-depleted peripheral blood lymphocytes as antigen-presenting cells. These modified antigen-presenting cells were then used to restimulate memory effector cells against NY-ESO-1 from the peripheral blood of cancer patients. Specific CD8(+) T cells thus sensitized were assayed on autologous B cell targets infected with a recombinant vaccinia virus encoding NY-ESO-1. Strong polyclonal responses were observed against NY-ESO-1 in antibody-positive patients, regardless of their HLA profile. Because the vectors do not cross-react immunologically, only responses to NY-ESO-1 were detected. The approach described here allows monitoring of CD8(+) T cell responses to NY-ESO-1 in the context of various HLA alleles and has led to the definition of NY-ESO-1 peptides presented by HLA-Cw3 and HLA-Cw6 molecules.

Alleles↗

['Microbial air pollutants'. Emission sources and preventive measures].

Already in the planning or monitoring phase, measures have to be realized for the reduction in emissions of bio-aerosols in biological waste treatment plants. For this purpose, operation-related measures (in open and partially closed plants) and technology-related measures (in closed plants with automatic ventilation) can be taken. A survey on the currently feasible measures for reduction is submitted. The realization has to be adapted to the individual site and type of plant. An enormous demand for examinations is envisaged in order to enable a qualified assessment of the emission behaviour of diverse waste air systems or process steps.

Air Microbiology↗

A probabilistic model for the failure frequency of underground gas pipelines.

A model is constructed for the failure frequency of underground pipelines per kilometer year, as a function of pipe and environmental characteristics. The parameters in the model were quantified, with uncertainty, using historical data and structured expert judgment. Fifteen experts from institutes in The Netherlands, the United Kingdom, Italy, France, Germany, Belgium, Denmark, and Canada participated in the study.

Algorithms↗

Vincristine, doxorubicin, cyclophosphamide, prednisone and etoposide (VACPE) in high-grade non-Hodgkin's lymphoma--a multicenter phase II study.

BACKGROUND: Patients with high-grade non-Hodgkin's lymphoma (NHL) can potentially be cured by intensive chemotherapy. However, many patients still die of their disease, which underscores the need to define patient groups with different long-term prognoses and for more effective and possibly risk-adapted treatment approaches. PATIENTS AND METHODS: In this phase II study we investigated the feasibility and efficacy of a polychemotherapy consisting of 2 mg vincristine (V) on day 1, 25 mg/m2 doxorubicin (A) days 1-3, 800 mg cyclophosphamide (C) day 1, 60 mg/m2 prednisone (P) days 1-7 and 120 mg/m2 etoposide (E) days 1-3. This cycle (VACPE) was repeated on day 22 for up to 5 cycles in stages I-III and 6 cycles in stage IV, respectively, followed by consolidating radiotherapy in 38/73 patients. A total of 75 patients with high-grade NHLs according to the Kiel classification were eligible, and 73 patients are evaluable for response. The predominant histological subtypes were centroblastic, pleomorphic T-cell and large-cell anaplastic lymphomas, 60% of the patients presented with stage III/IV, 55% with a poor performance status (ECOG > or = 2), 53% with B symptoms and 60% with a LDH level >200 U/l. RESULTS: 57/73 patients achieved CR (78%), and the overall response rate (CR-PR) was 95%. The median observation time is 40 months (10+-74+). The 1-, 3- and 5-year overall survivals for the entire VACPE group were 79%, 64% and 61%, respectively. Forty-one patients are in ongoing CR with a continuous complete remission rate (CCR) of 67%. Fourteen of the 16 patients who relapsed (88%) did so within the first 24 months. The predicted 1-, 3- and 5-year DFS for those patients who achieved CR is 83%, 67% and 67%, respectively. The early mortality was 3/73 (4.1%). In patients with reduced performance status the overall survival (OS) (ECOG > or = 2) was significantly reduced, with a predicted 1-, 3- and 5-year survival of 62%, 49% and 49% versus 100%, 84% and 77% in patients with favorable performance status, respectively (p = 0.001). The predicted overall survival in stages III/IV is worse than in early stages with a 1-, 3- and 5-year probability of 73%, 52% and 52% versus 90%, 86% and 78%, respectively (p = 0.02). Comparison of patient groups with cumulative risk factors shows a significant decrease in overall survival. Especially in patients with 0-2 risk factors versus those presenting with >2 risk factors, there is a significantly better 3- and 5-year survival (p = 0.002). In contrast to overall survival, there were no differences between the listed risk groups concerning the disease-free survival of complete responders. CONCLUSION: In conclusion, the VACPE regime is feasible and effective in high-grade NHLs and may also be administered on an outpatient basis. Despite encouraging data, however, a prospective randomized trial is warranted to define a possible superiority to standard CHOP. However, this regimen may be the basis for further randomized and risk adapted innovative approaches for high-grade NHLs.

Adolescent↗

[Air microbial burden at garbage sorting facilities].

At two german garbage sorting facilities, germ concentrations in the air were analyzed at different working environments (waste reception, manual sorting). At plant A, maximum concentrations of total bacteria (14700 CFU/m3), gram-negative bacteria (7279 CFU/m3) and moulds (> 84806 CFU/m3) occurred in the air at the final manual sorting belts. Referring to concentrations of total bacteria and moulds, concentrations in the air at the final sorting belts were significantly higher (p < 0.001) than at the other working environments. At plant B, the counts of total bacteria reached 7173 CFU/m3 in the air at the waste reception site and 5512 CFU/m3 at the manual sorting belt. Maximum concentrations for gram-negative bacteria were 247 resp. 206 CFU/m3 and 70919 resp. 60848 CFU/m3 for moulds. At the waste reception site, the aerial concentrations of total bacteria lay highly significantly (p < 0.001) and of moulds significantly (p < 0.05) above aerial concentrations at the manual sorting belt. As causes, an intensive mechanical pretreatment of recycle material at plant A and whirling up of sedimentary dust of the floor during manual sweeping of the material on to the transportation at plant B are discussed.

Air Microbiology↗

[Composting facilities. 2. Aerogenic microorganism content at different working areas of composting facilities].

At two composting facilities (plants D and E), contamination of the air with total bacteria and mould fungi, and in addition with gram-negative bacteria (only at plant D) was analyzed at different indoor sites and outdoor in the vicinity. Statistical validity of the determination of contents of microorganisms in air samples was guaranteed by the collection and analysis of 30 parallel samples. At plant D, total bacteria concentrations in outdoor air ranged from 106 to 15,618 CFU/m3 air (median: 495 CFU/m3 air), gram-negative bacteria concentrations ranged up to 71 CFU/m3 air (median: below the detection limit of 35 CFU/m3 air), and mould fungi reached 7,138 CFU/m3 air (median: 141 CFU/m3 air). Highest concentrations of total bacteria above the upper detection limit (> 84,806 CFU/m3 air, sample volume: 28.3 l) and of mould fungi (38,940 CFU/m3 air) occurred at the place where three months old compost was mixed, highest concentrations of gram-negative bacteria (14,134 CFU/m3 air) were measured during mixing of fresh compost (younger than 8 days). Maximum and median values of the examined microorganisms ranged so high that special protective means for personnel working directly beneath the mixing process seem to be necessary under hygienic aspects. Raw and clean air at the composting filter at plant D showed highly significant differences concerning air concentration of gram-negative bacteria and mould fungi, indicating a good separation efficiency for these types of microorganisms. Maximum and median values of gram-negative bacteria and mould fungi concentrations (all < 1,000 CFU/m3 air) measured in clean air behind the composting filter lie in the range of normal outdoor air. Merely total bacteria show statistical significant differences to outdoor air with median values of clean air of 1,979 CFU/m3 air (edge of filter) resp. 3,110 CFU/m3 air (upside the filter) and with maximum values of above 30,000 CFU/m3 air in each case. In the outdoor air at plant E, total bacteria concentrations ranged from 362 to 7,633 CFU/m3 air (median: 1,312 CFU/m3 air), mould fungi ranged from 115 to 4,072 CFU/m3 air (median: 345 CFU/m3 air). Highest concentrations of total bacteria and mould fungi (all analyses above the upper detection limit of 21,201 CFU/m3 air; sample volume: 113,2 l) occurred during shredding of a mixture of kitchen and green wastes and of shrubs. During experimental shredding of separately collected panty diapers air concentrations of total bacteria ranged from about 19,000 CFU/m3 air to > 21,201 CFU/m3 air.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Microbiology↗

[Composting facilities. 1. Microbiological quality of compost with special regard to disposable diapers].

At three different composting facilities, co-composting of used panty diapers with an addition of 10% (weight) to the usual plant input was investigated for various hygienic and microbiological parameters. In nearly any case, a sufficient degree of germ reduction above 99.9% could be observed by determination of reduction rates of B. subtilis spores. The concentrations of "total microorganisms" ranged from 3.9 x 10(5) to 3.3 x 10(11) colony forming units per gram compost (CFU/g) in composts without and from 3.3 x 10(5) to 4.7 x 10(9) CFU/g in composts with panty diapers in the input. The concentrations of "gram-negative bacteria" ranged from 3.3 x 10(4) to 1.3 x 10(9) CFU/g (without panty diapers) resp. from 3.3 x 10(5) to 3.5 x 10(8) CFU/g (with panty diapers), the concentrations of "fecal streptococci" from 1.7 x 10(3) to 7.7 x 10(7) CFU/g (without panty diapers) resp. from 1.4 x 10(4) to 1.4 x 10(8) CFU/g (with panty diapers). Facultatively pathogenic microorganisms showed a broad variety, but no common trend in composts with and without panty diapers in the input. Statistical validity of the determination of contents of microorganisms in compost samples was guaranteed by the collection and analysis of 20 parallel samples with an average sample mass of 10 to 15 kg. From the analyzed quantitative and qualitative hygienic-microbiological parameters, it can be concluded that no negative hygienic-microbiological effects, caused by the addition of 10% (weight) of used panty diapers in the input, have to be expected. Under the aspects of epidemiologic hygiene, composting of used panty diapers together with usual input materials seems to cause no increased risks under the tested conditions. Under the aspect of consumer protection, there is no increase in the risk of infection when using compost produced with addition of panty diapers, compared to compost produced without panty diaper addition to the input.

Bacillus subtilis↗

[Medical wastes. 2. Comparative studies of the microbial contamination of wastes from medical practices of different disciplines and household garbage].

Medical consulting room wastes of 7 disciplines were investigated quantitatively and qualitatively for nosocomial infective agents. 20-25 samples from each consulting room were examined for 3 months. The results were compared with those of household refuse and hospital wastes. The whole content of a waste bag was suspended without a preceding sorting and the eluate was microbiologically examined. The results of the investigations proved, that the germ concentration of the medical consulting room wastes was less than that of household refuse. The median for all investigated germ groups was less than 1 log(10)-step compared-to household refuse. The statistical analyses confirmed highly significant differences (p less than 0.001) for total germ concentration, thermoresistant obligate aerobic and facultative anaerobic bacteria and bacteria spores. Exceptionally the paediatric consulting room wastes show smaller differences (p less than 0.01) between the household refuse for obligate and facultative anaerobic bacteria, thermoresistant obligate and facultative anaerobic bacteria and bacteria spores and D-streptococci. From the comparison of total germ concentration for medical wastes from conservative disciplines and household refuse resulted that wastes from medical consulting rooms are less contaminated with nosocomial infective agents than household refuse and hospital wastes. In conclusion wastes from medical consulting rooms can, similar to hospital wastes, be disposed together with household refuse.

Bacteria↗

[Medical waste. 1. Microbiologic studies of wastes of various specialties at a large and small hospital in comparison to housekeeping waste].

Hospital wastes, similar to household refuse, from normal and high risk areas of a big and a smaller hospital were tested quantitatively and qualitatively for nosocomial infective agents. The results were compared with those of household refuse. 20-25 samples from care and operating wards were examined each for 3 months. The whole content of a waste bag was suspended without a preceding sorting. After this treatment the eluat was microbiologically examined. The results of the test proved that the germ concentration of the hospital waste was less or similar than that of household refuse. The median for gram negative rods in household refuse was e.g. 4 log10-steps higher than in wastes from operating wards. The statistical analysis confirmed these highly significant differences between the wastes from the high risk operating areas of the big and smaller hospital and the household refuse for all investigated bacteria groups. There are nearly no differences between the wastes from normal wards and from household refuse regarding germ concentration for different groups, e.g. gram negative rods or D-streptococci, and no higher germ concentration in any case. In conclusion hospital wastes must be disposed with special hygienic measures inside the hospital, outside the hospital they can be disposed together with household refuse.

Bacteria↗

Chloramphenicol/thiamphenicol and cycloheximide as tools for the measurement of mitochondrial protein synthesis in vitro during organogenesis of rat embryos.

1. A test system was developed to allow the measurement of protein synthesis in vitro in mitochondria from tissues which were accessible only in small quantities. The subcellular fractions which could be isolated are not purely mitochondrial but contain other particles as well, mainly microsomal, which are also active in protein synthesis. The following differences between mitochondrial and microsomal protein synthesis in vitro were used to measure selectively the mitochondrial portion in cell fractions sedimenting between 600 and 10000 X g: selective inhibition of mitochondrial protein synthesis by chloramphenicol/thiamphenicol selective inhibition of microsomal protein synthesis by cycloheximide kinetics of amino acid incorporation a medium favoring mitochondrial protein synthesis Activity of mitochondrial protein synthesis was based on measurements of cytochrome oxidase, a mitochondrial marker enzyme. 2. The technique developed was used for the evaluation of mitochondrial protein synthesis in mammalian embryonic tissues. It may equally well be applied to other tissues available in small amounts and in cases where the isolation of highly purified mitochondrial fractions is met with difficulty. 3. Comparing the rate of 14C-phenylalanine incorporation into mitochondrial protein from rat embryos at different stages of gestation, it was found that mitochondria from 11=day-old rat embryos exhibit an approximately 30-fold higher capacity for protein synthesis than those of day 13-16. On day 12 the capacity is 6 times higher than on the following days.

Animals↗